Methylprednisolone Administration for Acute Multiple Sclerosis Relapses
For acute MS relapses, administer 1000 mg methylprednisolone intravenously once daily for 3 consecutive days, infused over at least 30 minutes, which can be given orally with equivalent efficacy if the patient can tolerate oral medication. 1, 2
Dose and Duration
- Standard regimen: 1000 mg methylprednisolone daily for 3 days is the evidence-based dose for MS relapses 2, 3
- The FDA label specifies that for acute MS exacerbations, 160 mg daily for 1 week followed by 64 mg every other day for 1 month has been shown effective, though the 3-day high-dose regimen is more commonly used in current practice 1
- Treatment should be initiated within 15 days of relapse onset for optimal benefit 2
Route of Administration: IV vs Oral
Oral methylprednisolone 1000 mg daily is non-inferior to IV administration and should be considered first-line unless the patient cannot tolerate oral medication. 2
- A high-quality 2015 randomized controlled trial (COPOUSEP) demonstrated that oral methylprednisolone 1000 mg daily for 3 days was non-inferior to IV administration, with 81% vs 80% achieving improvement at 28 days 2
- The only difference: insomnia was more common with oral administration (77% vs 64%) 2
- Oral administration offers advantages in cost, convenience, and patient comfort without compromising efficacy 2
IV Preparation and Infusion Rate
When IV administration is chosen:
- Reconstitution: Use only Bacteriostatic Water for Injection with Benzyl Alcohol when reconstituting methylprednisolone sodium succinate 1
- Infusion rate: Administer 1000 mg IV over at least 30 minutes 1
- Critical safety warning: Cardiac arrhythmias and/or cardiac arrest have been reported following rapid administration of large IV doses (>0.5 gram over <10 minutes) 1
- Bradycardia has been reported during or after large dose administration, potentially unrelated to infusion speed 1
Dilution for IV Infusion
- After reconstitution, the solution may be added to 5% dextrose in water, isotonic saline solution, or 5% dextrose in isotonic saline solution 1
- From a microbiological standpoint, use immediately after preparation 1
- If not used immediately: chemical and physical stability is maintained for 4 hours at room temperature (<25°C) or 24 hours if refrigerated (2-8°C) 1
Alternative Dosing Considerations
- A 2019 pilot study suggested that a lower dose of 625 mg daily for 3 days may be non-inferior to 1250 mg daily, though the standard dose showed superior improvement at day 7 4
- However, stick with the established 1000 mg daily dose as this is the most widely validated regimen 2, 3
Common Pitfalls to Avoid
- Do not administer doses >0.5 gram over <10 minutes due to cardiac arrhythmia risk 1
- Do not assume IV is superior to oral—the evidence shows equivalence, and oral is more convenient 2
- Do not delay treatment beyond 15 days from relapse onset, as efficacy decreases with delayed initiation 2
- Do not use the standard Medrol dose pack (84 mg total over 6 days) for MS relapses—this is grossly inadequate 5
Monitoring During Treatment
- Inspect solution visually for particulate matter and discoloration before administration 1
- Monitor for cardiac symptoms during infusion, particularly bradycardia and arrhythmias 1
- Assess disability using Expanded Disability Status Scale (EDSS) at baseline, day 7, and day 28 2